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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
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More- Versus Less-Intensive Lipid-Lowering Therapy.

Toshiaki Toyota1, Takeshi Morimoto2, Yugo Yamashita3

  • 1Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan (T.T.).

Circulation. Cardiovascular Quality and Outcomes
|August 16, 2019
PubMed
Summary

Adding non-statin cholesterol-lowering drugs to statins significantly reduces cardiovascular events. More-intensive lipid-lowering therapy, including statins, ezetimibe, or PCSK9 inhibitors, proved more effective than less-intensive approaches.

Keywords:
PCSK9 inhibitorsezetimibelipidsmyocardial infarctionrisk factors

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Area of Science:

  • Cardiology
  • Pharmacology
  • Public Health

Background:

  • The comparative effectiveness of adding non-statin low-density lipoprotein cholesterol (LDL-C)-lowering agents to statins versus more-intensive statin therapy for cardiovascular risk reduction remains incompletely understood.
  • Atherosclerotic cardiovascular disease (ASCVD) poses a significant global health burden, necessitating optimized lipid-lowering strategies.

Purpose of the Study:

  • To systematically review and meta-analyze randomized controlled trials (RCTs) comparing more-intensive versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients at risk for ASCVD.
  • To evaluate the efficacy of different intensive LLT strategies, including intensified statin therapy, ezetimibe combination therapy, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy.

Main Methods:

  • A systematic review and meta-analysis of 23 RCTs involving 133,037 patients were conducted.
  • Studies compared more-intensive LLT (higher statin dose, statin + ezetimibe, or statin + PCSK9 inhibitor) against less-intensive LLT (lower statin dose or statin alone).
  • The primary outcome assessed was the odds of major adverse cardiovascular events (MACE), defined as the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization.

Main Results:

  • More-intensive LLT significantly reduced MACE compared to less-intensive LLT across the entire study population (odds ratio [OR], 0.84; 95% CI, 0.79-0.88).
  • All three intensive strategies demonstrated significant MACE reduction: intensified statins (OR, 0.83; 95% CI, 0.76-0.90), ezetimibe combination (OR, 0.90; 95% CI, 0.85-0.96), and PCSK9 inhibitors (OR, 0.81; 95% CI, 0.73-0.90).
  • The odds reduction for MACE per 20 mg/dL LDL-C reduction varied among strategies, with intensified statins showing 17.4%, ezetimibe 11.0%, and PCSK9 inhibitors 6.6% reduction.

Conclusions:

  • More-intensive LLT, encompassing intensified statin therapy, ezetimibe, and PCSK9 inhibitors, is associated with significant odds reduction for MACE in patients with atherosclerotic cardiovascular risk.
  • While all intensive strategies were effective, the magnitude of MACE reduction and the reduction per unit of LDL-C lowering differed across the therapeutic approaches.
  • These findings support the use of more-intensive LLT strategies for optimizing cardiovascular event risk reduction in high-risk patients.